Oncofetal fibronectin, a distinct class of adhesive extracellular matrix (ECM) molecules, has recently been associated with the biological processes of trophoblastic implantation, placentation, and chorionic membrane stability (Feinberg et al., Am J of Pathology 138:537-543 (1991); Feinberg and Kliman, Troph Res 7:167-179 (1993); Cunningham et al., eds. Williams Obstetrics 19th Edition. Norwalk, Conn.: Appleton and Lange, 122 (1993)). During pregnancy, oncofetal fibronectin is normally found within the trophoblast-associated ECM of the uteroplacental junction and chorion, (Feinberg et al., Am J of Pathology 138: 537-543 (1991); Feinberg and Kliman, Troph Res 7:167-179 (1993); Cunningham et al., eds. Williams Obstetrics 19th Edition. Norwalk, Conn.: Appleton and Lange, 122 (1993)) as well as in soluble form in amniotic fluid (Matsuura and Hakomori Proc Natl Acad Sci USA 82:6517-6521 (1985)).
The original identification of oncofetal fibronectins in pregnancy and tumor tissues was based on the isolation of a novel monoclonal antibody, FDC-6. Matsuura et al., U.S. Pat. No. 4,894,326 issued Jan. 16, 1990. A series of elegant manuscripts by Matsuura, Hakomori, and co-workers have demonstrated that FDC-6 binds to a specific O-linked N-acetygalactosaminylated hexapeptide epitope within the fibronectin type III connecting segment (IIICS) (Matsuura and Hakomori, Proc Natl Acad Sci USA 82:6517-6521 (1985); Matsuura et al., J Biol Chem 263: 3314-3322; Matsuura et al. (1988), J Biol Chem 264:10472-10476 (1989)). This binding site, which requires both the peptide backbone and the carbohydrate moiety to generate the epitope, is not found in high abundance in normal adult fibronectins. Thus, FDC-6 has been incorporated into a sensitive enzyme linked immunoassay5 for the clinical detection of cervicovaginal oncofetal fibronectin.
Detection of oncofetal fibronectin that is abnormally released into the cervix and vagina prior to 37 weeks of gestation has helped identify patients at high risk for preterm labor and delivery (Lockwood et al., N Engl J Med 325:669-74 (1991); Morrison et al., Am J Obstet Gynecol 168:538-542 (1993); Nageotte et al., Am J Obstet Gynecol 166:274 (1992) Lockwood et al., Am J Obstet Gynecol 169: 798-804 (1993); Creasy, Am J Obstet Gynecol 168:1223-30 (1993)).
It was found, however, that FDC-6 was not suitable for all diagnostic assays because FDC-6 was found to bind to 1-4% of circulating human plasma fibronectin from nonpregnant individuals. As a result, some diagnostic procedures were found to be hindered by false positives. This has been especially true with sensitive diagnostic assays of cervicovaginal FDC-6 reactive fibronectin perhaps due, in part, to overt or occult bleeding and the presence of plasma fibronectin.
Accordingly, novel antibodies for enhancing the specificity of oncofetal fibronectin diagnostic assays are greatly desired.